Rhabdomyolysis during concomitant ticagrelor and rosuvastatin: A breast cancer resistance protein-mediated drug interaction?
United States
Humans
Female
Rosuvastatin Calcium
/ adverse effects
Ticagrelor
/ adverse effects
ATP Binding Cassette Transporter, Subfamily G, Member 2
Neoplasm Proteins
/ metabolism
Drug Interactions
Organic Anion Transporters
/ metabolism
Rhabdomyolysis
/ chemically induced
Breast Neoplasms
/ drug therapy
drug-drug-interaction
myotoxicity
rhabdomyolysis
rosuvastatin
ticagrelor
Journal
British journal of clinical pharmacology
ISSN: 1365-2125
Titre abrégé: Br J Clin Pharmacol
Pays: England
ID NLM: 7503323
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
revised:
27
01
2023
received:
18
11
2022
accepted:
30
01
2023
medline:
19
6
2023
pubmed:
7
2
2023
entrez:
6
2
2023
Statut:
ppublish
Résumé
We present 3 patients diagnosed with rhabdomyolysis 1-6 months after the initiation of concomitant rosuvastatin and ticagrelor medication. A literature review and Food and Drug Administration adverse event reporting system revealed >40 reports of rhabdomyolysis during concomitant ticagrelor and rosuvastatin, including 3 with a fatal outcome. We show that ticagrelor inhibits breast cancer resistance protein-, organic anion transporting polypeptide (OATP) 1B1-, 1B3- and 2B1-mediated transport of rosuvastatin in vitro with half-maximal unbound inhibitory concentrations of 0.36, 4.13, 7.5 and 3.26 μM, respectively. A static drug interaction model predicted that ticagrelor may inhibit intestinal breast cancer resistance protein and thus increase rosuvastatin plasma exposure 2.1-fold, whereas the OATP-mediated hepatic uptake of rosuvastatin should not be inhibited due to relatively low portal ticagrelor concentrations. Taken together, concomitant use of ticagrelor with rosuvastatin may increase the systemic exposure to rosuvastatin and the risk of rosuvastatin-induced rhabdomyolysis. Further studies are warranted to investigate the potential pharmacokinetic interaction between ticagrelor and rosuvastatin in humans.
Substances chimiques
Rosuvastatin Calcium
83MVU38M7Q
Ticagrelor
GLH0314RVC
ATP Binding Cassette Transporter, Subfamily G, Member 2
0
Neoplasm Proteins
0
Organic Anion Transporters
0
Types de publication
Review
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2309-2315Informations de copyright
© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
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